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The development of new antibacterial agents and novel approaches is therefore extremely important. We set out to explore the potential of catalytic antibiotics as a new paradigm in antibiotics research. Herein, we describe our pilot study on the design, synthesis, and biological testing of a series of new derivatives of the natural aminoglycoside antibiotic neomycin\u2005B for their potential action as catalytic antibiotics. The new derivatives showed significant antibacterial activity against wild\u2010type bacteria and were especially potent against resistant and pathogenic strains including <jats:italic>Pseudomonas aeruginosa<\/jats:italic> and methicillin\u2010resistant <jats:italic>Staphylococcus aureus<\/jats:italic>. Selected compounds displayed RNase activity even though the activity was not as high and specific as we would have expected. On the basis of the observed chemical and biochemical data, along with the comparative molecular dynamics simulations of the prokaryotic rRNA decoding site, we postulate that the rational design of catalytic antibiotics should involve not only their structure but also a comprehensive analysis of the rRNA A\u2010site dynamics.<\/jats:p>","DOI":"10.1002\/cbic.201800549","type":"journal-article","created":{"date-parts":[[2018,11,25]],"date-time":"2018-11-25T22:10:27Z","timestamp":1543183827000},"page":"247-259","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Towards Catalytic Antibiotics: Redesign of Aminoglycosides To Catalytically Disable Bacterial Ribosomes"],"prefix":"10.1002","volume":"20","author":[{"given":"Boris","family":"Smolkin","sequence":"first","affiliation":[{"name":"The Edith and Joseph Fischer Enzyme Inhibitors Laboratory Schulich Faculty of Chemistry Technion\u2014Israel Institute of Technology  Haifa 3200003 Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina","family":"Khononov","sequence":"additional","affiliation":[{"name":"The Edith and Joseph Fischer Enzyme Inhibitors Laboratory Schulich Faculty of Chemistry Technion\u2014Israel Institute of Technology  Haifa 3200003 Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4583-1249","authenticated-orcid":false,"given":"Tomasz","family":"Pie\u0144ko","sequence":"additional","affiliation":[{"name":"Centre of New Technologies University of Warsaw  Banacha 2c 02-097 Warsaw Poland"},{"name":"Department of Drug Chemistry Faculty of Pharmacy with the Laboratory Medicine Division Medical University of Warsaw  Banacha 1a 02-097 Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Shavit","sequence":"additional","affiliation":[{"name":"The Edith and Joseph Fischer Enzyme Inhibitors Laboratory Schulich Faculty of Chemistry Technion\u2014Israel Institute of Technology  Haifa 3200003 Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valery","family":"Belakhov","sequence":"additional","affiliation":[{"name":"The Edith and Joseph Fischer Enzyme Inhibitors Laboratory Schulich Faculty of Chemistry Technion\u2014Israel Institute of Technology  Haifa 3200003 Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1464-5323","authenticated-orcid":false,"given":"Joanna","family":"Trylska","sequence":"additional","affiliation":[{"name":"Centre of New Technologies University of Warsaw  Banacha 2c 02-097 Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1427-2619","authenticated-orcid":false,"given":"Timor","family":"Baasov","sequence":"additional","affiliation":[{"name":"The Edith and Joseph Fischer Enzyme Inhibitors Laboratory Schulich Faculty of Chemistry Technion\u2014Israel Institute of Technology  Haifa 3200003 Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,12,21]]},"reference":[{"key":"e_1_2_7_1_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.12.4762-4765.2004"},{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.13.9.1159"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(10)78021-6"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpa.2008.01.028"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201701714"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1039\/B509022A"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1039\/c1ob06399e"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1039\/C4RA05751A"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr0301088"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1039\/a901140d"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1039\/c0dt00704h"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ica.2007.11.012"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1039\/b300332a"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0162-0134(03)00029-1"},{"key":"e_1_2_7_15_1","first-page":"435","author":"Takahashi S. 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